Usage Information
Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy
Abstract
Mechanisms of chimeric antigen receptor (CAR) T cell–mediated antitumor immunity and toxicity remain poorly characterized because few studies examine the intact tumor microenvironment (TME) following CAR T cell infusion. Axicabtagene ciloleucel is an autologous anti-CD19 CAR T cell therapy approved for patients with large B cell lymphoma. We devised multiplex immunostaining and ISH assays to interrogate CAR T cells and other immune cell infiltrates in biopsies of diffuse large B cell lymphoma following axicabtagene ciloleucel infusion. We found that a majority of intratumoral CAR T cells expressed markers of T cell activation but, unexpectedly, constituted ≤5% of all T cells within the TME 5 days or more after therapy. Large numbers of T cells without CAR were also activated within the TME after axicabtagene ciloleucel infusion; these cells were positive for Ki-67, IFN-γ, granzyme B (GzmB), and/or PD-1 and were found at the highest levels in biopsies with CAR T cells. Additionally, non-CAR immune cells were the exclusive source of IL-6, a cytokine associated with cytokine release syndrome, and were found at their highest numbers in biopsies with CAR T cells. These data suggest that intratumoral CAR T cells are associated with non-CAR immune cell activation within the TME with both beneficial and pathological effects.
Authors
Pei-Hsuan Chen, Mikel Lipschitz, Jason L. Weirather, Caron Jacobson, Philippe Armand, Kyle Wright, F. Stephen Hodi, Zachary J. Roberts, Stuart A. Sievers, John Rossi, Adrian Bot, William Go, Scott J. Rodig
Usage data is cumulative from March 2025 through March 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,432 | 594 |
| 228 | 140 | |
| Figure | 533 | 6 |
| Supplemental data | 86 | 11 |
| Citation downloads | 99 | 0 |
| Totals | 3,378 | 751 |
| Total Views | 4,129 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
